Laron Z, Kowadlo-Silbergeld A, Eshet R, Pertzelan A
Ann Clin Res. 1980 Oct;12(5):269-77.
Biological ineffectiveness of endogenous or exogenous growth hormone (GH) (i.e. a state or resistance) has been reported in several clinical conditions. The most typical form is Laron-type dwarfism, a hereditary disease which is clinically undistinguishable from isolated GH deficiency and which is characterized by high levels of plasma hGH but low somatomedin (SM). It is shown that the GH molecule binds normally to human liver receptors proving its normalcy. Thus the disease is due to an inability to generate active SM. States of resistance to exogenous GH by receptor occupancy exist when endogenous hormone is secreted in large amounts (newborns, acromegaly) or even normal amounts. Endorgan resistance to SM and GH such as in Pygmies represent an additional type. GH resistance is also induced by a rise in antibodies to GH by use of an impure or altered preparation or in a rare form of lack of immunotolerance to hGH, or by an enhancement of SM inhibitors as is seen in chronic renal failure or corticosteroid overdosage.
在多种临床情况下,已报道了内源性或外源性生长激素(GH)的生物学无效性(即抵抗状态)。最典型的形式是拉伦型侏儒症,这是一种遗传性疾病,临床上与孤立性生长激素缺乏症无法区分,其特征是血浆人生长激素水平高但生长介素(SM)水平低。研究表明,生长激素分子能正常与人肝受体结合,证明其正常性。因此,该疾病是由于无法产生活性生长介素所致。当内源性激素大量分泌(新生儿、肢端肥大症)甚至正常分泌时,存在因受体占据而对外源性生长激素产生抵抗的状态。终末器官对生长介素和生长激素的抵抗,如在俾格米人中,代表了另一种类型。使用不纯或改变的制剂导致抗生长激素抗体增加,或罕见的对人生长激素缺乏免疫耐受性,或慢性肾衰竭或皮质类固醇过量时生长介素抑制剂增加,也会诱导生长激素抵抗。